脑深部电刺激双侧伏核对吗啡成瘾大鼠复吸行为的影响

目的 研究脑深部电刺激双侧伏核核心部对吗啡成瘾大鼠复吸行为的影响.方法 手术前筛选大鼠,筛选后大鼠随机分为空白组、空白电刺激组、吗啡组、吗啡假手术组、吗啡电刺激组.电极植入7d后采用隔日递增原则皮下注射吗啡(5mg/kg起始,每次递增5mg/kg,至20mg/kg稳定)建立大鼠吗啡成瘾模型.通过改进后的DBS电路进行电刺激,刺激参数为130Hz、150A、60s、1 h/d、14d.干预前后变化由条件位置偏爱实验检测.复吸行为采用小剂量吗啡(3 mg/kg)诱导,24h后再次检测CPP.数据统计采用two-way ANOVA,组间比较用Bonferroni方法.结果 ①完成CPP训练后,吗啡组、吗啡假手术组、吗啡电刺激组三个组的CPP评分为(155.87±20.45)s、(107.33 ± 18.10)s、(135.45±22.09)s,与前两组均有明显差异[与空白组(-70.34±15.40)s比较t值和P值分别为:t=9.45,P＜0.01;t=6.94,P＜0.01;t=8.04,P＜0.01].②7天DBS后,吗啡电刺激组大鼠CPP评分与吗啡组(t=4.21,P＜0.01)、吗啡假手术组(t=1.10,P＜0.05)差异明显.14d DBS后差异更加明显(t=5.15,P＜0.01;t=3.92,P＜0.01).③给予小剂量吗啡诱导复吸后,吗啡电刺激组CPP评分小于吗啡组(t=4.04,P＜0.01)和吗啡假手术组(t=4.13,P＜0.01)组,且与空白组(-53.50 ± 11.10)s(t=2.60,P＞0.05)差异无显著性,但与空白电刺激组(t=3.70,P＜0.01)仍差异有显著性.结论 DBS双侧伏核核心部不仅可以干预吗啡成瘾大鼠的CPP行为,而且能抑制小剂量吗啡诱导的复吸行为.

Abstract：

Objective To investigate the influence on the behavior of withdrawal and relapse after deep brain stimulation of bilateral nucleus accumbens in morphine-dependent rats. Methods The rats with a strong unconditioned preference were discarded in preconditioning test, the selected rats were distributed into five groups randomly. After operation,morphine hydrochloride was injected subcutaneously into SD rats for 12 days (once every day,initial 5 mg/kg,increasing by 5 mg/kg per time,stable in 20 mg/kg ). A modified electrical circuit was used to procedure the DBS,the parameter was 130 Hz,150 A,60 s,l h/d,14 d. CPP test was used to exam the effect of DBS. A minor morphine dose (3 mg/kg) was injected to induce the behavior of relapse, and CPP was tested again after 24 h. Two-way ANOVA was performed on the data with Bonferroni posttest. Result ①After CPP training,CPP score of group morphine, morphine + sham and morphine + DBS was ( 155. 87 ± 20. 45 ) s, (107.33 ± 18.10)s,(135.45 ±22.09)s,and had significant difference with group of control( ( -70.34 ± 15.40) s)(t = 9.45,P＜0.01; t = 6.94,P＜0.01;t = 8.04,P＜0.01).②After 7 days' DBS,the CPP score in group of morphine + DBS reduced significantly compared to group of morphine( t = 4.21, P＜0.01) and morphine + sham( t=1.10, P＜0.05).0n the 14th day,there was more pronounced reduction ( t = 5. 15, P＜0.01; t = 3.92, P＜ 0.01). ③ 24 hours after the minor morphine dose was injected,the CPP score in morphine + DBS didn't increase significantly, and had significant difference with group of morphine ( t = 4.04, P＜0.01) and morphine + sham ( t= 4. 13, P＜0.01). Conclusion DBS bilateral nucleus accumbens in morphine-dependent rats can interfere the behavior of morphine-induced CPP and relapse.     

Change of p16~(INK4a) and PNCA Protein Expression in Myocardium after Injection of hIGF-1 Gene Modified Skeletal Myoblasts into Post-infarction Rats

This study examined the change of p16^INK4a and PNCA protein expression in myocardium after injection of hIGF-1 gene modified skeletal myoblasts into post-infarction rats. HIGF-1 gene modified skeletal myoblasts （hIGF-1-myoblasts） were injected into hind limb muscles of 18 post-infraction rats （experimental group）. Primary-myoblasts were injected into 18 post-infraction rats （control group） and 12 non-infarction rats （sham group）. Expression of p16INK4a and PCNA pro- tein in myocardiums were separately detected immunocytochemically 1, 2 and 4 weeks after the inuection. The level of hIGF-1 and rIGF-1 protein in serum and myocardium were detected by en- zyme-linked immunosorbent assay （ELISA）. Compared with the sham group, the percentage of p^16INK4a and PCNA positive cells reached a peak after 1 week in the control group and the experimental group （P〈0.01）. Moreover, the percentage of p16^INK4a-positive cells in the experimental group was lower than in control group whereas the percentage of PCNA-positive cells was lower in the control group than in the experimental group （P〈0.01）. The percentage of p16^INK4a-positive cells in the experimental group and the percentage of PCNA-positive cells in the control group were close to that in the sham group from the 2nd week （P〉0.05）. ELISA analysis disclosed that the myocardium level of rIGF-1 protein increased gradually in the controls and especially in the experimental group （P〈0.01）. The serum level of rIGF-1 decreased significantly in post-infraction rats, but these conditions were improved in the experimental group （P〈0.01）. The hIGF-1 protein in serum and myocar- dium were detected from the 1st week to the 4th week in the experimental group. Statistical analysis revealed significant associations of myocardium level of hIGF-1 protein with expression of p^16INK4a and PCNA protein （r=–0.323, P〈0.05; r=0.647, P〈0.01）. It is concluded that genetically hIGF-1-myoblast provides a means for constant synthesis and re     

二甲胺四环素在蛛网膜下腔出血中保护作用的研究

Objective To investigate the effect of minocycline on early brain injury (EBI) following subarachnoid hemorrhage(SAH) in rats. Methods SAH was induced by the filament perforation model in male Sprague Dawley rats. SD rats(n=77) were randomly assigned to sham (n=22), SAH+vehicle (n=28), and SAH+minocycline (n=27) groups. Minocycline (135mg/kg) or equal volume of vehicle was administered 1 h after SAH induction. Mortality, neurological scores, brain edema were evaluated 24 h after SAH. Cell apoptosis were examined by TUNEL staining, and the expression of caspase-3 and Bcl-2 was assayed by Western blot at the same time point. Results The mortality was 21.4% in SAH+vehicle group, 18.5% in the SAH+minocycline group, while no death was observed in sham-operated rats; there was no significant difference in mortality between SAH+vehicle and SAH+minocycline groups (P＞0.05), but the mortality in these two groups was much higher than that in shamgroup(P＜0.05). The water content of brain was significantly increased in the SAH+vehicle group (80.00±0.16)% compared with that in sham group [(79.13±0.08)%, P＜0.05]. Minocycline treatment markedly reduced brain water content (79.36±0.07)% compared with that in SAH+vehicle group (P＜0.05). Caspase-3 levels were markedly increased in SAH+vehicle group (1.53±0.24) compared with sham group (1.00±0.21). Minocycline treatment significantly reduced caspase-3 levels, compared to SAH+vehicle group (1.11±0.18, P＜0.05). A significant decrease in Bcl-2 expression was observed in SAH+vehicle group(0.65±0.03) compared with the sham group (1.00±0.12). The treatment of minocycline upregulated the expression of Bcl-2,compared to SAH+vehicle group (0.93±0.13, P＜0.05). TUNEL-positive cells were increased in the cortex of SAH+vehicle rats,compared to sham group [(31.50±3.70)%, P＜0.05]. Minocycline treatment significantly reduced the number of TUNEL positive cells, compared to SAH+vehicle group [(14.25±2.50)%, P＜0.05]. Conclusion Minocycline may reduce early brain injury after subarachnoid hemorrhage in rats by inhibiting cell apoptosis, which is associated with down-regulation of caspase-3 and up-regulation of Bcl-2.     

Effect of pre-electroacupuncture on p38 and c-Fos expression in spinal dorsal horn of rats suffering from visceral pain

Background The purpose of this study was to investigate effects of pre-electro acupuncture (EA) on pain behaviors, p38 phosphorylation, and c-Fos protein and mRNA expression in colonic wall and spinal dorsal horn of rats suffering from visceral pain, and to evaluate the signaling regulatory mechanism of electro acupuncture’s analgesic effect. Methods Rats were randomized into the Con group, the Con+EA group, the VP group and the VP+EA group (n=8, each). 40μL of 5% Formalin solution was injected into colon of the rats, to establish visceral pain model. EA was applied to the bilateral Jiaji acupoints for 20min before the visceral pain, with a parameter set of continuous wave (20Hz) and the intensity that the rats shook their whiskers but did not scrabble (≤1 mA). The visceral pain score was recorded, and the expression of p38 and c-Fos protein was detected by Western blot analysis. The expression of c-Fos mRNA was examined by the real-time quantitative PCR method. Results Rats in the VP group immediately presented obviously visceral pain behaviors after being injected with Formalin, and the p38 activity and the expressions of c-Fos protein and mRNA in colonic wall and spinal dorsal horn were higher in the VP group than in the Con group (P<0.05); While rats in the VP+EA group delayed their presence of visceral pain behaviors, and the p38 activity and the expression of c-Fos protein and mRNA were lower in the VP+EA group than in the VP group (P<0.01). Conclusions Pre-electroacupuncture of Jiaji acupoint has prophylactic analgesic effects on rats suffering from visceral pain, and at least in part, involves p38 signal transduction pathway.     

Huoxue Anxin Recipe(活血安心方)Promotes Myocardium Angiogenesis of Acute Myocardial Infarction Rats by Up-Regulating miR-210 and Vascular Endothelial Growth Factor

Objective: To investigate the microR NAs(miR NAs) expression profile of acute myocardial infarction(AMI) rats and the regulating effects of Huoxue Anxin Recipe(活血安心方, HAR) on angiogenesis-related miR NAs and genes. Methods: Forty-five Wistar rats were randomly assigned to 3 groups according to a random number table: sham, AMI, and AMI+HAR groups(15 in each group). AMI rats were established by ligation of the left descending coronary artery. HAR was intragastrically administered to rats of the AMI+HAR group for successive 21 days since modeling, meanwhile the same volume of 0.9% normal saline was administered to rats of the sham and AMI groups. Doppler echocardiography was used for noninvasive cardiac function test. Hematoxylin and eosin staining was used to observe the histopathological change. miR NAs expression profile was detected by quantitative realtime polymerase chain reaction(qR T-PCR). The mR NA and protein expressions of vascular endothelial growth factor(VEGF), and a target gene of miR-210 was further detected by qR T-PCR and Western blot, respectively. The microvessels density of myocardium was evaluated by CD31 immunostaining. Results: Compared with the sham group, ejection fraction(EF) and fractional shortening(FS) values were decreased significantly in the AMI group(P0.01), while the infarction area and the interstitial collagen deposition were increased obviously. As for the AMI+HAR group, EF and FS values were increased significantly(P0.05 vs. AMI group), and the infarction area was reduced and the interstitial collagen deposition were alleviated significantly. Total of 23 miR NAs in the AMI group expressed differently by at least 1.5 folds compared with those in the sham group; 5 miR NAs in the AMI+HAR group expressed differently by at least 1.5 folds compared with those in the AMI group. Among them, miR-210 was low in the AMI group and high in the AMI+HAR group. The relative mR NA and protein expressions of VEGF were decreased significantly in the AMI group(P0.05 vs. sham group), and increased significantly in the AMI+HAR group(P0.01 vs. AMI group). CD31 expression area and optical intensity were decreased significantly in the AMI group(P0.05 vs. sham group), and increased significantly in the AMI+HAR group(P0.01 vs. AMI group). Conclusions: HAR could reduce the infarction area, alleviate the interstitial fibrosis and improve the cardiac function of AMI rats. Those effects could be related to promoting myocardium angiogenesis of HAR by up-regulating miR-210 and VEGF.     

Effects of tetramethylpyrazine on cardiac function and mortality rate in septic rats

Objective:To study the effects of tetramethylpyrazine(TMP)on cardiac function and mortality rate in septic rats.Methods:Fifty male Sprague-Dawley rats were randomized into a sham-operation group (sham group,n=10),normal saline group(NS group,n=20),and TMP group(n=20).The rats in the NS and TMP groups underwent cecal ligation and puncture(CLP)to induce sepsis.Rats in the NS group were injected with NS(10 mL/kg)immediately after CLP and 6 h after CLP.Rats in the TMP group were injected with TMP (10 mg/kg)at the same time points.Twenty-four hours after modeling,the mortality rates were observed in each group.Cardiac function and serum concentration of tumor necrosis factorα(TNF-α)were also tested. The correlation between TNF-αand the ejection fraction(EF)was observed.Left ventricle specimens were reserved for histomorphologic study.Results:Compared with the sham group,the NS and TMP groups had decreased EF values and increased mortality rates and serum TNF-αlevels(P<0.05).The TMP group had a comparatively lower mortality rate and TNF-αlevel and a higher EF value compared with the NS group(P<0.05). Histomorphology indicated that myocardial inflammation in the TMP group was mild compared with that in the NS group.There was a negative correlation between TNF-αlevel and EF value(r=-0.583,P=0.000).Conclusion: TMP could reduce the mortality rate of septic rats and had certain protective effects on cardiac function.     

Effects of Kaixin Jieyu Decoction (开心解郁汤) on Behavior and Glial Fibrillary Acidic Protein Expression in Cerebral Hippocampus of A Rat Vascular Depression Model

Objective:To explore the effects and anti-depression mechanisms of Kaixin Jieyu Decoction(开心解郁汤,KJD).Methods:The rat vascular depression(VD) model was established by ligation of bilateral common carotid arteries(LBCCA) combined with chronic unpredictable mild stress(CUMS).Forty Wistar rats were randomly divided into sham,VD model,VD + high-dose KJD[15.4 g/(kg·d) of crude drug],VD + medium-dose KJD[7.7 g/(kg·d) of crude drug],and VD + fluoxetine[2.4 mg/(kg·d)]groups(r=8 in each group),and the treatments lasted for 21 days.Changes of behavior and hippocampus pathology were observed.The level of glial fibrillary acidic protein(GFAP)protein and mRNA in hippocampus was detected respectively by immunohistochemistry and real-time polymerase chain reaction.Results:Compared with the sham group,rats in model group showed a variety of behavioral obstacles,including a significant reduction in sucrose consumption percentage,horizontal and vertical activity scores in open-field tests(P0.05 or P0.01),pathological damage like neuronal degeneration,necrosis,and a significant decrease of GFAP protein and mRNA in hippocampus(P0.01);compared with the model group,rats in the high-dose KJD group,medium-dose KJD group and fluoxetine group obtained notable higher behavioral scores,and pathological injury lessened in hippocampus with a increased expression of GFAP protein and mRNA(P0.05 or P0.01);compared with the medium-dose KJD group and fluoxetine group,GFAP mRNA in highdose KJD group expressed higer(P0.05).Conclusion:LBCCA combined with CUMS may cause depression-like behavioral changes resulting in the VD model of rats whose depression state can be ameliorated by KJD,and the mechanism of cerebral protection is related possibly with promoting expression of GFAP in hippocampus.     

Hyperbaric oxygen intervention on expression of hypoxia inducible factor-1α and vascular endothelial growth factor after spinal cord injury models in rats

【Abstract】Objective: To observe the change of expression of Hypoxia inducible factor-1α (HIF-1α) and Vascular endothelial growth factor (VEGF) after spinal cord injury at different time and to investigate the Neuroprotective mechanism of hyperbaric oxygen (HBO) on spinal cord injury (SCI) in rats. Methods: 160 adult Sprague-Dawley rats, weighing between 250g and 300g,were randomly assigned to 4 experimental groups (n=40 per group). SCI group: SCI was created with special NYU impactor of Allen’s by a 25gram-centimeter (GCM) impacting energy on T10 of the spinal cord. SCI HBO group: hyperbaric oxygen therapy after spinal cord injury model was established. Sham operation（SH）group: only laminectomy of T10 and no impact on the spinal cord was done. SH HBO group: hyperbaric oxygen therapy after sham operation. The hindlimb functional recovery was evaluated using Basso Beattie Bresnahan (BBB) score and the expression of HIF-1α and VEGF were observed with fluorescent quantitation PCR and Western-Blot method of six rats picked randomly from each group at different times of 1, 3, 7 and 14 days after operation. Result: Rats in the SCI group and SCI HBO group were paralyzed completely after operation with BBB 0-1 score. Rats in the SH group and SH HBO group could walk after sham operation with BBB 20-21 score. The BBB scores of rats in SCI HBO group was higher than that in SCI group at 7d and 14d time point obviously (P＜0.05);The expression of HIF-1α and VEGF in SCI group and SCI HBO group was higher than in SH group and SH HBO group at any time point obviously (P＜0.05);while the SCI HBO group presented the least expression of HIF-1α at 3d,7d and 14d time points (P＜0.05) and more expression of VEGF at 7d and 14d (P＜0.05) than that of the SCI group with significant difference. Conclusion: The experimental research showed HBO could improve the hind limb functional recovery after SCI in rats;The higher expression of HIF-1α and VEGF could promote repair of damaged spinal cord after SCI;The elevation and duration of the expression of VEGF and the expression of HIF-1α by HBO intervention maybe inversely related in the repair of damaged spinal cord and neuroprotective effect.     

Baicalein Attenuates Severe Polymicrobial Sepsis via Alleviating Immune Dysfunction of T Lymphocytes and Inflammation

Objective:To investigate the effect of baicalein on polymicrobial sepsis-induced immune dysfunction and organ injury.Methods:A sepsis model was induced in Sprague-Dawley rats via caecal ligation and puncture(CLP).Specific pathogen free rats were randomly divided into a sham group,CLP group and CLP+baicalein(Bai)group(n=16 each).Rats in the CLP+Bai group were intravenously injected with baicalein(20 mg/kg) at 1 and10 h after CLP.Survival rate,bacterial load,and organ damage were assessed.Then eac...     

The Property of Nao Yi-an Granule(脑溢安颗粒) in Increasing Nestin Immunoreactive Neural Stem Cells in Rat Brains with Intracerebral Hemorrhage

Objective: To explore changes of neural stem cells (NSCs) following intracerebral hemorNYA's therapeutic mechanism Methods: Sixty rats were randomly divided into three groups, the sham operation control group, the ICH group and the NYA-treated group. Except those in the sham operation control group, all other rats were replicated to ICH models by stereotactical injection of collagenase type Ⅶ into their globus pallidus. After modeling, the rats in the NYA-treated group were administered with NYA at the given instead. The behavioral test was used to evaluate neurological deficit and immunohistochemical method was used to detect Nestin expression, the special marker for neural stem cells. Results: The ICH animals showed notable placing deficit in forlimbs from day 1 to day 28 after modeling. The deficit in the NYA-treated group was similar to that of the ICH group, but the former got recovered better than the latter from day 21 to 28, with significant difference shown (P＜0.05). Nestin-positive cells (N cells) could be seen around the hemotoma from day 2 on in the ICH group, the number of which gradually increased from day 4 to 7 ( P＜0.01) and reached the peak on day 14 (P＜0.05), but reduced significantly on day 28 (P＜0.01). Compared with that of the ICH group at the same time points, there was no significant difference in number of N cells in the NYA group on day 2 and 4, but it reached the peak earlier on day 7(P＜0.01), with the level significantly higher than that in the ICH group(P＜0.01), and this high level lasted to day 14. Conclusion: NYA could promote the recovery of behavioral deficit in collagenase type Ⅶ-induced ICH rats, and increase the number of nestin-immunoreactive NSCs, suggesting that its effect on NSCs may be one of its pharmaceutical mechanisms in treating ICH.     

麻疹的双相移位研究进展

近年新生儿、婴儿、成人麻疹患者逐年增加,临床表现一般仍较典型,成年人麻疹患者全身中毒症状较重。麻疹抗体检测结果阳性是主要的诊断依据。麻疹发病的双相移位的机理可能是,免疫保护力不足,婴儿出生时麻疹抗体力低。孕期母传胎的麻疹抗体减弱,母经乳汁传给婴儿的抗体减弱,成人麻疹抗体水平逐年下降。预防措施是怀孕前给予育龄妇女麻疹疫苗接种,鼓励母乳喂养,麻疹疫苗计划免疫适当提前,在成人追加麻疹疫苗的免疫,加强病毒变异的研究等。     

正常增殖期子宫内膜细胞增生状态的定量观察

以＾３氢－胸腺嘧啶核苷放射自显影法及ＨＥ染色，观察并分别测定了１８例正常子宫内膜增殖中期，１５例增殖晚期的腺上皮细胞或间质细胞的标记指数、分裂指数。结果显示：子宫内膜增殖晚期腺上皮细胞或间质细胞之ＬＩ均明显高于增殖中期。同时，增殖晚间质细胞之ＭＩ也明显高于增殖中期，即此两种细胞在增殖晚期中增生明显，其增生状态初步获得了定位定量测定的正常值。     

人工全髋关节置换术的手术配合

目的：介绍人工全髋关节置换术的手术配合做法;方法：主要在手术配合的六个方面,解决防感染、防栓塞等问题。结果：30例人工全髋关节置换术均获成功,结论：手术配合是护士责任心和基本功的全面体现,对提高手术效果有至关重要的影响。     

80例局限性银屑病误诊原因分析

本文报告80例局限于小腿或手或足的银屑病。均经皮肤组织病理检查确诊。因部位比较特殊。受多种理化因素影响,使皮疹形态发生轻重程度不同的变化,常看不到典型损害,因而误诊为神经性皮炎,湿疹,慢性皮炎及癣等。作者对误诊原因进行了分析后,提出了鉴别诊断方法。     

腰椎间盘突出症再次手术的原因分析

目的解决腰椎间盘突出症手术中神经压迫。方法对1980～1998年再手术资料进行统计分析,讨论分析再手术原因,再次手术前影像学检查,观察病理变化以确定再手术方法。结果对11例随访6个月～1年,优7例(68．4％),良3例(36．8％),差1例(2．8％)。结论初次手术前详细查体和分析X线片,术中用导尿管和神经剥离探查,尽量避免髓核遗留,手术范围不宜太大,尽量减少对软组织和脊柱结构的破坏,避免形成硬膜囊与神经根粘连而致单纯形疤痕。     

妊娠晚期重度妊高征的监测

重度妊高征表现为高血压、蛋白尿、浮肿等症状 ,严重可以导致母婴死亡。对妊娠足月的重度妊高征 ,可以根据其临产与否及宫颈条件 ,立即决定其为阴道分娩或是剖宫产术。对于妊娠晚期的重度妊高征 ,因其胎龄不足月 ,胎儿生长发育及胎肺成熟度情况需通过一定时间的治疗 ,根据其病情变化来决定其治疗方案或终止妊娠的时机[1,2 ] 。这就需要我们对这一阶段的治疗进行监测 ,防止母儿并发症的发生。现将 2 0 0 0年至今我院收治妊娠晚期重度妊高征 30例的监测结果回顾分析如下。1　资料和方法1.1　研究对象　选择孕 31～ 36周重度妊高征 30例 ,其中 …     

尿微量白蛋白检测在继发性肾脏疾病中的临床意义

目的探讨尿微量白蛋白（m-Alb）检测在继发性肾脏疾病中的临床意义。方法采用Beckman Immage全自动特种蛋白分析仪对糖尿病组、高血压组、心脏病组患者进行了m-Alb测定,同时与健康组结果作对比。结果m-Alb检测糖尿病组为3.7±5.26mg/dl,高血压组为7.5±8.18mg/dl,心脏病组为7.8±3.76mg/dl,健康组为0.66±0.48mg/dl,各试验组m-Alb增高百分率为糖尿病组48.9%,高血压组37.5%,心脏病组26.9%。结论尿蛋白阴性的糖尿病、高血压、心脏病患者进行m-Alb检测,可以监测病程的进展。